胃癌中ArgBP2基因差异表达的机制及其功能研究

项目名称： 胃癌中ArgBP2基因差异表达的机制及其功能研究

项目编号： No.30800415

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 李妍

作者单位： 中国医科大学

项目金额： 20万元

中文摘要： ArgBP2是一个新的衔接子蛋白家族成员，不仅参与肌动蛋白细胞骨架重建、细胞迁徙和成形、细胞增殖和存活以及细胞信号传导，而且作为一个潜在的抑癌基因在多种肿瘤的发生发展中起到重要作用。我们前期研究发现ArgBP2基因在不同分化程度的胃腺癌组织中与癌旁正常组织相比表达均有明显下调，同时通过芯片检测发现在胃癌中ArgBP2受到胃癌相关转录因子ZCWCC1的负性调控作用，说明ArgBP2可能是与胃癌发生发展相关的重要基因。本研究中我们首先通过报告基因、Real-time PCR及Western blot等方法证实了ZCWCC1对Argbp2的下调作用。接着构建稳定转染的Argbp2的胃癌细胞系，检测了Argbp2对胃癌细胞生长能力、致瘤性和细胞侵袭力的影响。同时发现，在胃癌细胞中，组蛋白去乙酰化修饰参与Argbp2的转录抑制，并通过体内外实验证实了ZCWCC1和HDAC4的相互作用。另一方面CA9是通过芯片检测发现在胃癌中受到ZCWCC1负性调控作用的另一个靶向基因，我们的研究发现组蛋白去乙酰化参与了ZCWCC1对CA9的负性调控。

中文关键词： ArgBP2;ZCWCC1;抑癌基因；转录调控；CA9

英文摘要： Argbp2 is a novel adaptor protein which is not only involved in cytoskeleton reorganization, cell migration and formation,cell proliferation and survival and signaling transduction,but also plays an important role in various tumorigenesis as an tumor suppressor gene. In our previous study we found that Argbp2 is down-regulated in different differentiation gastric cancer comparing with normal tissue. Furthermore we performed a DNA microarray hybridization and found Argbp2 mRNA to be obviously down-regulated when ZCWCC1 which is gastric cancer associated gene was overexpressed. It is suggested that Argbp2 is an important gene in gastric tumorigenesis. In our study we first proved that Argbp2 is down-regulated by ZCWCC1 using luciferase assay, Real-time and Western blot assays. Then we constructed stable transfection Argbp2 gastric cancer cell line to detect the influence of growth ability, oncogenicity and migration ability of gastric cancer cell. In addition ,we also found that histone deacetylation is involved in ZCWCC1-mediated down-regulation of Argbp2. In vivo and in vitro assays showed ZCWCC1 interacts with HDAC4. At the same time CA9 is another gene which is down-regulated by ZCWCC1 through DNA microarray hybridization. And histone deacetylation is involved in ZCWCC1-mediated down-regulation of CA9.

英文关键词： ArgBP2;ZCWCC1;tumor suppressor gene；gene regulation；CA9